1. Field of the Invention
The present invention relates generally to compositions, methods and kits for treating Alzheimer's disease by administration of cells or cell derivatives. In particular, the invention provides administering cells or cell derivatives to a patient to reduce the accumulation of plaque proteins as well as provide support factors to reduce neuronal cell death. The invention also provides administering cells or cell derivatives to a patient to treat symptoms of Alzheimer's disease.
2. Description of Related Art
Alzheimer's disease is the most common cause of dementia in North America and Europe. Generally, Alzheimer's disease is a common and complex disorder characterized by adult-onset progressive dementia. The disease usually begins after age 65, and the risk of Alzheimer's disease increases with age. Indeed, approximately 10 percent of all persons over the age of 70 have significant memory loss and more than half of these individuals have Alzheimer's disease. The prevalence of dementia in individuals over the age of 85 is estimated to be about 25-45%. Further, Alzheimer's disease is believed to be the fourth leading cause of death in elderly adults.
A record number of people are becoming elderly in the next few decades. Unless effective methods for prevention and treatment are developed by the pharmaceutical and medical industries, Alzheimer's disease may reach epidemic proportions by the middle of the next century. Because of increasing longevity, the occurrence of Alzheimer's disease in the elderly presents a tremendous medical, economic and social problem facing the health care industry today.
Alzheimer's disease is a degenerative disease of the brain from which there is no recovery. The disease attacks nerve cells in all parts of the cortex of the brain, as well as some of the surrounding structures and tissues. Typically, Alzheimer's disease begins with subtle and poorly recognized failure of memory. The early symptoms of Alzheimer's disease may be overlooked because such symptoms resemble signs of natural aging. These symptoms include forgetfulness, loss of concentration, unexplained weight loss and motor problems, including mild difficulties in walking. In healthy individuals, similar symptoms can result from fatigue, grief or depression, illness, vision or hearing loss, the use of alcohol with certain medications, or simply the inability to remember complex details at one time. Accompanying sensory problems, such as hearing loss and a decline in reading ability, as well as general physical debility indicate a short survival time. Other symptoms include confusion, poor judgment, language disturbance, agitation, withdrawal, and hallucinations. Some patients may develop seizures, Parkinsonian-type features, decreased muscle tone, myoclonus, incontinence and mutism. The patient may also exhibit symptoms such as inability to perform routine tasks, loss of language skills, inability to plan, and personality changes. Over time, these changes become so severe and impairing that the patient loses all memory and mental functioning to the point of complete central nervous system (CNS) collapse and cessation of regulated circulatory and respiratory function.
Clinically, Alzheimer's disease is a neuropathological disease. Recognized clinical signs include progressive dementia and cerebral cortical atrophy, which can be established by neuroimaging studies. In addition, neuropathological findings usually include microscopic A-beta amyloid neuritic plaques, intraneuronal neurofibrillary tangles and amyloid angiopathy. Studies indicate that Alzheimer's disease is associated with cerebral cortical atrophy, histological findings of beta amyloid plaques and findings of intraneuronal neurofibrillary tangles within the cortical regions of the brain.
Neurofibrillary tangles are tangled fibers, which are the damaged remains of microtubules, within the cortical region of the brain, that support the structure allowing the flow of nutrients through nerve cells (neurons). Beta amyloid is an insoluble protein which is a fragment of a larger protein (APP). APP itself appears to be important in nerve protection. Should the enzyme involved in cutting APP into fragments of beta amyloid fail to function, APP has been shown to form sticky patches called neuritic plaques, which decrease neuronal function and signal transmission within the brain. Generally, such neuritic plaques are found on the outside of nerve cells surrounded by debris of dying neurons.
In addition, high levels of beta amyloid are associated with reduced levels of the neurotransmitter acetylcholine. Neurotransmitters are chemical messengers in the brain that transmit various signals, messages, and neurochemical information within the various regions of the CNS. Acetylcholine is part of the cholinergic system, which is essential for memory and learning, and is progressively destroyed in patients suffering from Alzheimer's disease. Thus, it is theorized that beta amyloid in the form of neuritic plaques causes a decrease in the neurotransmitter, acetylcholine, leading to progression of Alzheimer's disease.
Currently, Alzheimer's disease treatment is based on managing disease symptomology for each individual's disease progression. Although there are drugs for treating Alzheimer's disease, there is no cure for the disease. Treatments include drugs that alter neurotransmitter availability in the CNS. For instance, some drugs increase acetylcholine in the brain, such as acetylcholinesterase inhibitors, work as dopamine receptor antagonist, and noncompetitive NMDA receptor antagonists. Other drugs are used to treat the aggression and psychosis of Alzheimer's patients.
Currently available treatments have side effects, including nausea, diarrhea, hepatotoxicity, abdominal cramping, ulcers, gastrointestinal bleeding, orthostatic hypotension, drowsiness, dizziness, sexual dysfunction, and insomnia. At times, the side effects are so severe that the physician ceases treatment.
Given the current limitations in treating Alzheimer's disease, there exists a need for alleviating Alzheimer's disease symptoms in individuals that is cost effective, has minimal potential for side effects, and positively increases memory, cognitive function, and ability to perform daily living activities.